尘肺伴肺癌微量元素检查分析

目的探讨粉尘与肺癌的发病关系。方法应用扫描电镜、Ｘ线能谱分析仪和电子探针,对２２例尘肺伴肺癌的肺内粉尘元素进行了观察、检测和分析。结果铝、硅元素明显高于非癌组,铜、锌偏低,差异有显著意义（Ｐ＜０．０５）。结论尘肺伴肺癌内的元素过多或过少,其比值改变在致癌方面可能起着重要作用。     

滋养细胞肿瘤患者血清微量元素的变化

采用原子吸收光谱法检测１６例滋养细胞肿瘤患者治疗前后血清微量元素铜、锌、锰和铬的含量，结果表明，滋养细胞肿瘤患者血清铜水平和铜／锌比值均显著高于正常未孕对照组（Ｐ〈０．０１）。经手术和ＡＣＭ三联序贯化疗后，随着病情的完全缓解，血清铜水平和铜／锌比值则明显下降（Ｐ〈０．０１），我们认为血清铜水平和铜／锌比值与滋养细胞肿瘤的病情和疗效有关。     

Serum trace element levels in patients with bladder cancer

Trace elements are essential components of biological structures, but they can be toxic at concentrations beyond those necessary for their biological functions. In the present study, groups of 35 patients with bladder cancer and 34 healthy volunteer controls were measured for trace elements using a furnace atomic absorption spectrophotometer. Serum levels of Cd, Ni and Co were increased (p<0.05) and Mn and Zn were decreased (p<0.05) in patients with bladder cancer. In the present study, a relationship was seen between the level of trace elements and the occurrence of bladder cancer, suggesting that an increase in the serum level of Cd, Ni, Co and a decrease in the levels of Zn and Mn might be important causes of bladder cancer occurrence; however, defining such a cause-and-effect relationship needs several prospective studies to be done, which seems necessary with regard to the high prevalence of this cancer.     

预处理化疗增强CIK细胞对Lewis肺癌的抑制作用

目的 观察预处理化疗在小鼠Lewis肺癌模型中对细胞因子诱导的杀伤细胞(cytokine - induced killer cells,CIK cells)的抗肿瘤活性的增强作用,并探讨介导此增效作用的机制.方法 建立C57BL/6小鼠Lewis肺癌模型,以紫杉醇( Paclitaxel,PTX)联合顺铂(Cispla...     

顺铂以T细胞依赖性方式增强ClK细胞的抗肿瘤作用

目的 观察顺铂预处理化疗联合细胞因子诱导的杀伤细胞( cytokine - induced killer cells,CIK cells)对小鼠CT - 26结肠癌的抑制作用,并探讨介导顺铂免疫调节效作用的机制.方法 分别建立BALB/c野生鼠或BALB/c nu/nu裸鼠CT - 26结肠癌模型,以顺铂(Cispla...     

Toenail trace element status and risk of Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study

Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable. Our study aimed to examine toenail trace element status and risk of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Toenail clippings from each hallux were obtained from 638 participants of the FINBAR (Factors Influencing the Barrett's Adenocarcinoma Relationship) study comprising 221 healthy controls, 98 reflux oesophagitis, 182 BO and 137 OAC cases. The concentrations of eight toenail trace elements were determined using instrumental neutron activation analysis. Using multivariable adjusted logistic regression analysis, odds ratios (OR) and 95% confidence intervals (CIs) were calculated within tertiles of trace element concentrations. A twofold increased risk of BO was observed, but not OAC, among individuals in the highest tertile of toenail zinc status OR 2.21 (95% CI, 1.11-4.40). A higher toenail selenium status was not associated with risk of OAC OR 0.94 (95% CI, 0.44-2.04) or BO OR 0.89 (95% CI, 0.37-2.12). A borderline significant increased risk of BO was detected with a higher toenail cobalt concentration, OR 1.97 (95% CI, 1.01-3.85). No association was found between toenail levels of chromium, cerium, mercury and OAC or BO risk. This is the first case-control study to investigate a variety of trace elements in relation to OAC and BO risk. Despite antioxidant and proapoptotic properties, no associations were found with selenium. Higher concentrations of toenail zinc and cobalt were associated with an increased BO risk, but not OAC. These findings need confirmation in prospective analysis.     

Dietary trace element intake and liver cancer risk: Results from two population‐based cohorts in China

Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997–2013) and men (2002–2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case–control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow‐up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35–0.73; p_trend = 0.001). Further adjustment for hepatitis B virus infection in the nested case–control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21–0.69; p_trend < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.     

Preconditioning chemotherapy with paclitaxel and cisplatin enhances the antitumor activity of cytokine induced-killer cells in a murine lung carcinoma model

Adoptive cell therapy involving the use of ex vivo generated cytokine-induced killer cells (CIKs) provides a promising approach to immunotherapy. However, the therapeutic activity of CIKs is limited by the immunosuppressive factors active in the host. It has become increasingly apparent that manipulation of the recipient immune system with the preconditioning regimen is essential to guarantee the antitumor effect of subsequent adoptive cell therapy. In our study, paclitaxel (PTX) and cisplatin (DDP) were used as preconditioning drugs combined with CIKs to illustrate the potential mechanisms underlying the synergic antitumor effect against Lewis lung cancer cells in vitro and in vivo. We found that 3LL cells displayed an increased sensitization to CIKs-induced lysis after treatment with PTX or DDP in vitro. Significant inhibition of tumor growth was observed in mice treated with combinatorial chemo-immunotherapy with respect to untreated or single regimen treated ones. Prior chemotherapy markedly enhanced the intratumoral accumulation of CD3(+) T lymphocytes and the homing of CIKs to the spleen and tumor. Moreover, the frequencies of intratumoral and splenic regulatory T cells (Tregs) were significantly decreased after chemotherapy pretreatment. Our findings provide a new rationale for combining immunotherapy and chemotherapy to induce a synergistic antitumor response in patients with lung cancer.     

Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models

The frequent overexpression of the hyaluronan receptors CD44 and RHAMM in cancer cells opens the door for targeting by the naturally-occurring high-M(r) hyaluronan. This is the first time effective in vivo tumor targeting is reported for mitomycin C (MMC) loaded inside nano-sized hyaluronan-liposomes (denoted tHA-LIP). The severe adverse effects of free MMC made it a rational candidate for an effective targeted carrier. In vitro, loading MMC inside tHA-LIP increased drug potency 100-fold, in cells overexpressing, but not in cells underexpressing, hyaluronan receptors. Both types of liposomes were non-toxic and reduced MMC-related toxicity in healthy C57BL/6 mice. In 3 tumor models, BALB/c bearing C-26 solid tumors; C57BL/6 bearing B16F10.9 or (separately) D122 lung metastasis, tHA-LIP were long-circulating, 7-fold and 70-fold longer than nt-LIP and free MMC, respectively. tHA-LIP-mediated MMC accumulation in tumor-bearing lungs was 20% of injected dose, compared to 0.6% and 4% with free drug and nt-LIP, respectively. Tumor-free lungs showed low accumulation, irrespective of drug formulation. Key indicators of therapeutic responses, tumor progression, metastatic burden and survival, were superior (p < 0.001) in animals receiving MMC-loaded tHA-LIP, no treatment, MMC-loaded nt-LIP and free drug. In conclusion, tHA-LIP perform as tumor-targeted carriers, with promising prospects for treatment of tumors overexpressing hyaluronan receptors.     

Flavone acetic acid increases the antitumor effect of hyperthermia in mice.

The combined effects of flavone acetic acid (FAA), a synthetic flavonoid, and hyperthermia on B16 melanoma cells were investigated. In vitro, FAA alone at concentrations below 100 micrograms/ml was not cytotoxic with a 60-min exposure at 37 degrees C. Hyperthermia at 43 degrees C for 60 min enhanced the cytotoxicity of FAA only at concentrations over 100 micrograms/ml. Inhibition of the growth of B16 melanoma solid tumor by FAA and/or hyperthermia was examined in vivo. FAA (100-200 mg/kg) inhibited tumor growth in a dose-dependent manner. The combined treatment of FAA (200 mg/kg) and hyperthermia (43 degrees C, 15 min) significantly inhibited tumor growth compared to a treatment of FAA or hyperthermia alone. The maximum antitumor effect of FAA combined with hperthermia was obtained when FAA was administered 2 or 4 h before heat. The significantly increased cytotoxicity of FAA combined with hyperthermia seems to relate to specific decreases in tumor blood flow, a reduction in tumor pH, and an increased tumor temperature, without altering pH in the normal tissues. This combined treatment of FAA and hyperthermia warrants further study for treating subjects with solid tumors.     

Pharmacological properties and antitumor activity of a preparation diiodo-benzo-tepa in experiments]

Experimental data on the pharmacokinetics, toxicity, antitumor activity of the antitumor drug diiodo-benzo-TEPA are reported.     

乳腺肿瘤患者血清中九种微量元素的石墨炉原子吸收测定及相关分析

目的　探讨乳腺良恶性肿瘤及健康妇女血清中微量元素含量及其相关关系。方法　用石墨炉原子吸收光谱法测定 2 13名健康妇女、36例乳腺良性瘤和 38例乳腺恶性瘤手术前后血清中 Zn、Fe、Cu、Mn、Pb、Cd、Cr、Ni和 Mo九种微量元素的含量。结果　三组血清中有五种元素有显著差异 ,其中血清 Zn、Cu、Ni和 Fe的含量乳癌患者明显高于对照组 ,血清 Mo则乳癌患者低于对照组 ,而且血清 Zn、Cu、Ni随病情发展而升高 ,血清 Mo则相反。乳癌患者血清 Cu/ Zn值 (1.4g)高于健康妇女 (1.30 )。结论无论元素的含量还是元素与元素间的相关性 ,乳腺癌、乳腺良性肿瘤和健康妇女三组之间都有明显的差异     

Carbon tetrachloride-induced increase in the antitumor activity of cyclophosphamide in mice: A pharmacokinetic study

Summary Carbon tetrachloride is an hepatotoxin that depresses hepatic microsomal cytochrome P-450 and other enzyme activities. Cyclophosphamide is an anticancer drug that is activated by hepatic microsomal cytochrome P-450, while the products of cyclophosphamide metabolism by cytochrome P-450 can be metabolized by other hepatic enzymes. Carbon tetrachloride pretreatment has been found to increase the in vivo antitumor activity of cyclophosphamide against murine leukemia P-388. Carbon tetrachloride did not, however, affect the direct cytotoxicity of cyclophosphamide or 4-hydroxycyclo-phosphamide to cells in culture. Pharmacokinetic studies in mice revealed a delayed plasma disappearance of cyclophosphamide after carbon-tetrachloride pretreatment with an apparent initial half-time of 20.4 min compared to 9.0 min in non carbon-tetrachloride-pretreated mice. Plasma levels of total alkylating activity and plasma 4-hydroxycyclophosphamide increased more slowly and reached a lower peak, but were maintained for a longer time period in mice pretreated with carbon-tetrachloride than in untreated mice. The half-life for plasma elimination of 4-hydroxycyclophosphamide in untreated mice was 12 min and in carbon-tetrachloride-pretreated mice 27 min. There was, however, no difference in the area under the curve for either plasma total alkylating activity or plasma 4-hydroxycyclophosphamide between the two groups. It is suggested that prolonged exposure of tumor cells to 4-hydroxycyclophosphamide might be responsible for the increased antitumor activity of cyclophosphamide following carbon-tetrachloride pretreatment.     

Variation of urinary and serum trace elements (Ca, Zn, Cu, Se) in bladder carcinoma in China

Backgrounds: Deficiency or excess of trace elements can induce body metabolic disorders and cellulargrowth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elementsin bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach.Methods: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthypersons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc[Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzedby independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzedby logistic regression. Results: The results showed urinary Ca, Zn and serum Cu levels of the study group tobe significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group weresignificantly lower (P<0.05) than those of control group. Conclusion: There were higher urinary Zn and serumCu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder,leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factorsfor bladder carcinoma in China.     

回族血清中微量元素含量与胃癌的相关性研究

目的探讨回族血清中微量元素含量与胃癌的关系。方法采用原子吸收分光光度法对回族胃癌患者和回族非胃癌对照人群血清中锌(Zn)、铜(Cu)、铁(Fe)、镁(Mg)、钙(Ca)、锰(Mn)、镍(Ni)元素含量进行检测,并用SPSS统计软件对实验结果进行配对t检验分析。结果回族胃癌病例组血清中Cu、Cu/Zn、Mn均比对照组高,而Zn、Fe、Ca、Mg、Ni的含量低于对照组。配对t检验结果显示,血清中Cu、Zn、Cu/Zn、Ca、Mg含量差异有统计学意义(P<0.05)。结论回族胃癌的发生、发展与血清内微量元素变化密切相关。高Cu、Cu/Zn比值高以及低Zn、低Ca、低Mg是回族胃癌发生的危险因素。     

Activation and antitumor activity of CPT-11 in plasma esterase-deficient mice

Purpose: To examine the antitumor activity and the pharmacokinetics of CPT-11 (irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) in a plasma esterase-deficient scid mouse model, bearing human tumor xenografts. Experimental design: Plasma carboxylesterase (CE)-deficient mice were bred with scid animals to develop a strain that would allow growth of human tumor xenografts. Following xenotransplantation, the effect of the plasma esterase on antitumor activity following CPT-11 administration was assessed. In addition, detailed pharmacokinetic studies examining plasma and biliary disposition of CPT-11 and its metabolites were performed. Results: In mice lacking plasma carboxylesterase, the mean SN-38 systemic exposures were approximately fourfold less than that observed in control animals. Consistent with the pharmacokinetic data, four to fivefold more CPT-11 was required to induce regressions in human Rh30 xenografts grown in esterase-deficient scid mice, as opposed to those grown in scid animals. Additionally, the route of elimination of CPT-11, SN-38, and SN-38 glucuronide (SN-38G) was principally in the bile. Conclusions: The pharmacokinetic profile for CPT-11 and its metabolites in the esterase-deficient mice more closely reflects that seen in humans. Hence, these mice may represent a more accurate model for antitumor studies with this drug and other agents metabolized by CEs.     

Indomethacin augmented antitumor activity of 5-fluorouracil in meth-a induced mice

Background This study used an ascitic fluid tumor model to assess antitumor effects of indomethacin (INN) and its enhancing effect on the antitumor activity of 5-fluorouracil (5FU). Methods Each (monotherapy) or both agents (combined therapy) were administered IP to BALB-c mice on alternate days. Antitumor activity was determined by survival of the experimental animals. Results INN (25 (μg/kg IP) improved the survival of the experimental animals significantly (P<0.005) when compared to the nonmedicated controls. The INN was shown to augment the antitumor activity of 5FU significantly at doses of 2.5 (P<0.005) and 10 (P<0.005) mg/kg IP, compared to 5FU monotherapy at each dose. Carcass weight was significantly higher (P<0.01–0.05) in the combination therapy groups than in the controls. This effect was the result of a less marked decrease in food intake, although there was no significant difference in carcass weight between single and combined therapies. Conclusion INN was shown to exert its antitumor effect and to augment the antitumor activity of 5FU which led to the improved survival of mice bearing ascitic tumors. This evidence suggests a potential role for INN as an adjunct to standard chemotherapy.     

Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice

As a single agent the ERBB1 inhibitor, gefitinib (Iressa; ZD1839) showed minimal activity against a panel of 10 pediatric tumor xenografts that do not express the ERBB1 receptor. However, combined with irinotecan (CPT-11), significantly greater than additive activity was observed in four of eight models (P < 0.05), and the combination showed enhanced activity against three additional tumor lines. Breast cancer resistance protein (ABCG2), a transporter that confers resistance to SN-38 (the active metabolite of irinotecan), was readily detected in six of nine xenograft models examined by immunohistochemistry. In vitro gefitinib potently reversed resistance to SN-38 only in a cell line that overexpressed functional ABCG2. However, overexpression of ABCG2 did not decrease accumulation nor increase the rate of efflux of [(14)C]gefitinib. On the basis of these results and the distribution of Abcg2 in mouse tissues, we assessed the ability of gefitinib to modulate irinotecan pharmacokinetics. Oral gefitinib coadministration resulted in no change in clearance of intravenously administered irinotecan. However, gefitinib treatment dramatically increased the oral bioavailability of irinotecan after simultaneous oral administration. It is concluded that gefitinib may modulate SN-38 activity at the cellular level to reverse tumor resistance mediated by ABCG2 through inhibiting drug efflux and may be used potentially in humans to modulate the oral bioavailability of a poorly absorbed camptothecin such as irinotecan.     

肺癌组织、癌旁组织及良性肺组织中七种微量金属元素水平的研究

目的 探讨微量元素在肺癌组织、癌旁组织及良性肺组织中的浓度及其变化规律。方法 利用原子吸收光谱法(atomic absorption spectrometry，AAS)对19例肺癌患者的肺癌组织和癌旁组织、9例肺部良性疾病患者的肺组织中的镉(cadmium，Cd)、铅(1ead，Ph)、铬(chromium，Cr)、锰(manganese，Mn)、镍(nickel，Ni)、铜(cuprum，cu)、锌(zinc，Zn)等七种元素进行了含量分析，采用同一元素在癌组织与癌旁组织的浓度比值判断此元素在肺癌发生、发展中的意义。结果 癌组织中Cu、Ph含量高于癌旁组织，癌旁组织又高于正常组织；癌旁组织中Cd、Cr、Mn、Ni、Zn含量高于肺癌组织；Ph元素主要积聚在肺癌组织；Ni元素主要积聚在癌旁组织。结论 不同肺组织中微量元素的含量存在差异，表明微量元素含量的变化与肺癌发生、发展有一定的关系。     

Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC cells and normal cells by measuring growth, death, cell cycle progression, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models.Piperlongumine killed HNC cells regardless of p53 mutational status but spared normal cells. It increased ROS accumulation in HNC cells, an effect that can be blocked by the antioxidant N-acetyl-L-cysteine. Piperlongumine induced selective cell death in HNC cells by targeting the stress response to ROS, leading to the induction of death pathways involving JNK and PARP. Piperlongumine increased cisplatin-induced cytotoxicity in HNC cells in a synergistic manner in vitro and in vivo. Piperlongumine might be a promising small molecule with which to selectively kill HNC cells and increase cisplatin antitumor activity by targeting the oxidative stress response.